Findings to help in design of drugs against virus causing childhood illnesses

Date:

March 21, 2013

Source:

Purdue University

Summary:

New research findings may help scientists design drugs to treat a virus infection that causes potentially fatal brain swelling and paralysis in children. The virus, called enterovirus 71, causes hand, foot and mouth disease, and is common throughout the world.

Share:

Total shares:

FULL STORY

New research findings may help scientists design drugs to treat a virus infection that causes potentially fatal brain swelling and paralysis in children.

The virus, called enterovirus 71, causes hand, foot and mouth disease and is common throughout the world. Although that disease usually is not fatal, the virus has been reported to cause fatal encephalitis in infants and young children, primarily in the Asia-Pacific region.

Currently, no cure exists for the infection.

New findings show the precise structure of the virus bound to a molecule that inhibits infection. The findings are detailed in a paper appearing this week in Proceedings of the National Academy of Sciences.

Rossmann is co-author of a paper with Purdue postdoctoral research associate Pavel Plevka; research scientist Rushika Perera; postdoctoral research associate Moh Lan Yap; Jane Cardosa, a researcher at Sentinext Therapeutics in Malaysia; and Richard J. Kuhn, a professor and head of Purdue's Department of Biological Sciences.

The researchers had previously used a technique called X-ray crystallography to determine the virus's precise structure. A small molecule called a "pocket factor" is located within a pocket of the virus's protective shell, called the capsid. When the virus binds to a human cell, the pocket factor is squeezed out of its pocket resulting in the destabilization of the virus particle, which then disintegrates and releases its genetic material to infect the cell and replicate.

Researchers led by Rossmann have developed antiviral drugs for other enteroviruses such as rhinoviruses that cause the common cold. The drugs work by replacing the pocket factor with a molecule that binds more tightly than the real pocket factor, inhibiting infection.

In the new work, the researchers obtained a near-atomic-scale resolution three-dimensional structure of enterovirus 71 binding with an inhibitor called WIN 51711.

"We show that the compound stabilizes the virus and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release," Rossmann said. "Our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs."

At a resolution of 3.2 angstrom, the images show nearly atomic-scale structural features.

Hand, foot and mouth disease, an infection most common among young children, sometimes arises in a daycare setting. Of the 427,278 cases of the disease recorded in mainland China between January and May 2010, 5,454 cases were classified as severe, with 260 deaths, according to the World Health Organization.

The research was supported by the National Institutes of Health and the U.S. Department of Energy.

Story Source:

The above post is reprinted from materials provided by Purdue University. The original item was written by Emil Venere. Note: Materials may be edited for content and length.

Purdue University. "Findings to help in design of drugs against virus causing childhood illnesses." ScienceDaily. ScienceDaily, 21 March 2013. <www.sciencedaily.com/releases/2013/03/130321133227.htm>.

Purdue University. (2013, March 21). Findings to help in design of drugs against virus causing childhood illnesses. ScienceDaily. Retrieved August 2, 2015 from www.sciencedaily.com/releases/2013/03/130321133227.htm

Purdue University. "Findings to help in design of drugs against virus causing childhood illnesses." ScienceDaily. www.sciencedaily.com/releases/2013/03/130321133227.htm (accessed August 2, 2015).

July 31, 2015  Resettlement projects in the Amazon are driving severe tropical deforestation, according to new research. Widely hailed as a socially responsible and 'innocuous' strategy of land redistribution, ... read more

July 29, 2015  Viewing aquarium displays led to noticeable reductions in blood pressure and heart rate, a research team found in the first study of its kind. They also noted that higher numbers of fish helped to ... read more

July 31, 2015  A new study examines how consuming the concentrated extract of thylakoids found in spinach can reduce hunger and cravings. Thylakoids encourage the release of satiety hormones, which is very ... read more

July 30, 2015  The behavior of fruit flies, which are commonly used in laboratory experiments, is altered by electric fields, new research shows. The research indicates that the wings of the insects are disturbed ... read more

July 31, 2015  Starvation early in life can alter an organism for generations to come, according to a new study in nematodes. The epigenetic effects are a 'bet-hedging strategy.' Famine survivors are smaller and ... read more

July 31, 2015  The humble butterfly could hold the key to unlocking new techniques to make solar energy cheaper and more efficient, pioneering new research has shown. By mimicking the v-shaped posture adopted by ... read more

Sep. 19, 2014  Does your child have Enterovirus 68 or just a bad cold? It can be hard to tell the difference between the two, but an infectious diseases specialist suggests how parents should treat their kids’ ... read more

Jan. 29, 2014  Researchers have discovered a potential treatment for a viral infection that causes potentially fatal brain swelling and paralysis in children. The findings also point to possible treatments for ... read more

Oct. 28, 2010  Scientists have completed the first major review of diagnostic methods and treatments for a rapidly evolving virus that causes hand, foot and mouth disease in children. The virus, called enterovirus ... read more